Acid-base extraction

Acid-base extraction is a procedure using sequential liquid-liquid extractions to purify alkaloids from crude extracts. The product is largely free of neutral and acidic or basic impurities. It is not possible to separate chemically similar acids or bases using this simple method.

Theory

The fundamental theory behind this technique is that salts, which are ionic, tend to be water-soluble while neutral molecules tend not to be.

The addition of an acid to a mixture of an organic acid and base will result in the acid remaining uncharged, while the base will be protonated. If the organic acid, such as a carboxylic acid, is sufficiently strong, its self-ionization can be suppressed by the added acid.

Conversely, the addition of a base to a mixture of an organic acid and base will result in the base remaining uncharged, while the acid is deprotonated to give the corresponding salt. Once again, the self-ionization of a strong base is suppressed by the added base.

The acid-base extraction procedure can also be used to separate very weak acids from stronger acids and very weak bases from stronger bases as long as the difference of their pK_a (or pK_b) constants is large enough. Examples are:

• Very weak acids with phenolic OH groups like sorbic acid (pK_a around 4 - 5)
• Very weak bases like caffeine or dimethyltryptamine (pK_b around 3 - 4)

Usually the pH is adjusted to a value roughly between the pK_a (or pK_b) constants of the compounds to be separated. Weak acids like sodium hydroxide (NaOH) are used for strongly alkaline conditions.

Technique

Usually, the mixture is dissolved in a suitable solvent such as evaporation of the solvent yields the product.

Limitations

The procedure works only for acids and bases with a large difference in solubility between their charged and their uncharged form. The procedure does not work for:

• glycine which tend to be water soluble at most pH.
• Very lipophilic amines that do not easily dissolve in the aqueous phase in their charged form, e.g triphenylamine and trihexylamine.
• Very lipophilic acids that do not easily dissolve in the aqueous phase in their charged form, e.g fatty acids.
• Lower amines amines like triethanolamine which are miscible or significantly soluble in water at most pH.
• Hydrophilic acids like phosphoric acid.

Alternatives

Alternatives to acid-base extraction including:

• filtering the mixture through a plug of alumina — charged salts tend to remain strongly adsorbed to the silica gel or alumina
• ion exchange chromatography can separate acids, bases, or mixtures of strong and weak acids and bases by their varying affinities to the column medium at different pH.

See also

• Separating funnel
• Multiphasic liquid
• Extraction
• Alkaloid
• Chromatography, a more powerful but more complex procedure to separate compounds